ROLE OF NITRIC-OXIDE ON SYSTEMIC AND SPLA NCHNIC HEMODYNAMIC DISTURBANCES IN AN EXPERIMENTAL-MODEL OF PORTAL-HYPERTENSION

Recent experimental studies have suggested that an increase in the syn thesis of nitric oxide, a powerful vasodilator secreted by endothelial cells, plays a role in the hemodynamic disturbances associated to por tal hypertension. The present study was addressed to investigate the e ffects of L-NNA (a specific inhibitor of nitric oxide) on systemic and splanchnic hemodynamics in portal hypertensive rats, induced by parti al portal vein ligation. Intravenous infusion of L-NNA (50 ug/Kg/min) significantly increased systemic blood pressure and decreased cardiac output as measured by radiolabeled microspheres. A significant increas e in systemic and splanchnic vascular resistance was also observed in L-NNA-treated rats; whereas portal blood flow decreased significantly, L-NNA did not modify portal pressure. Pretreatment with L-arginine (3 00 mg/Kg, iv) prevented the hemodynamic changes induced by L-NNA. Simi lar values of endotoxin levels were detected in both groups of animals . In the control group, L-NNA caused a mild but significant increase o f mean arterial pressure; no significant changes on the other hemodyna mic parameters were observed. These results suggest that an increase i n endogenous synthesis of nitric oxide may play an important role in h emodynamic disturbances associated with chronic portal hypertension.